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Subtle differences in the pathogenicity of SARS-CoV-2 variants of concern B.1.1.7 and B.1.351 in rhesus macaques

Vincent J Munster1, Meaghan Flagg1, Manmeet Singh1

  • 1Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.

Science Advances
|October 22, 2021
PubMed

Insights

New SARS-CoV-2 variants like B.1.1.7 and B.1.351 were compared in rhesus macaques. The B.1.351 variant showed reduced pathogenicity, suggesting evolution favors transmissibility over increased disease severity.

Area of Science:

  • Virology
  • Immunology
  • Comparative Pathology

Background:

  • Emergence of SARS-CoV-2 variants of concern (VOCs) raises global health concerns regarding transmissibility, pathogenicity, and vaccine efficacy.
  • Animal models are crucial for evaluating phenotypical changes in SARS-CoV-2 variants, controlling for confounding factors.
  • Previous studies have highlighted the D614G substitution's role in increased viral fitness.

Purpose of the Study:

  • To compare the pathogenicity and replication of SARS-CoV-2 variants of concern (VOCs) B.1.1.7 and B.1.351 against a D614G-containing B.1 isolate.
  • To assess the in vivo immune response, including cytokine and chemokine profiles, elicited by these different SARS-CoV-2 strains in a relevant animal model.
  • To determine if increased transmissibility or pathogenicity is the primary driver of SARS-CoV-2 evolution.

Main Methods:

  • Rhesus macaques were inoculated with SARS-CoV-2 isolates: B.1 (D614G), B.1.1.7, and B.1.351.
  • Clinical disease, viral replication in the respiratory tract (lungs, nasal swabs), and lung histopathology were assessed.
  • Cytokine and chemokine levels in bronchoalveolar lavage fluid and nasal samples were measured at specific time points post-inoculation.

Main Results:

  • The B.1.1.7 variant exhibited clinical disease and respiratory tract replication similar to the D614G B.1 isolate.
  • In contrast, B.1.351 inoculation led to lower clinical scores, reduced lung viral titers, and attenuated lung lesions.
  • Upregulation of cytokines and chemokines was observed in bronchoalveolar lavage fluid for D614G and B.1.1.7, and in nasal samples only for B.1.1.7, but not for B.1.351.

Conclusions:

  • The B.1.1.7 variant demonstrates comparable pathogenicity to the D614G B.1 SARS-CoV-2 isolate in rhesus macaques.
  • The B.1.351 variant exhibits reduced pathogenicity compared to both D614G B.1 and B.1.1.7 strains.
  • SARS-CoV-2 evolution under selective pressures appears to prioritize transmissibility and immune evasion over increased pathogenicity.

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